The role of FOXO1/PPARγ in atrazine-induced hepatic lipid metabolism disorders.

As one of the most prevalently employed herbicides worldwide, atrazine (ATR) is widespread in the environment and is able to enter and impair the human body. Hepatic lipid metabolism disorders can be triggered by exposure to ATR. However, the underlying mechanism remains unclear. We performed a differential gene expression analysis using the NAFLD-related datasets GSE89632 and GSE160016 downloaded from the GEO database, both with the human liver as the samples. Then the GO and KEGG pathway enrichment analyses were performed. It was discovered that the FOXO1/PPARγ pathway might play a crucial role in hepatic lipid metabolism disorders. To confirm the hypothesis, forty 8-week-old male Wistar rats were randomly average exposed to different concentrations of ATR (0, 0.5, 5 and 50 mg/kg/d) by intragastric administration for 90 days. Then the liver tissue were isolated for histopathological observation; the levels of lipids were assessed by colorimetry; the expression of mRNA and protein was identified by Real-Time PCR and western blot. The findings demonstrated that the ATR-treated groups had higher levels of TC and TG in the liver; TC level in the serum was increased but TG level decreased. Besides, the expression of FOXO1, PPARγ, FASN, FABP4 and CD36 was also elevated. A correlation was observed between the lipid metabolism levels and the expression of FOXO1/PPARγ pathway genes. These results suggested that ATR can induce hepatic lipids accumulation by upregulating the expression of FOXO1/PPARγ. This study can offer insightful information for preventing and controlling risks related to agricultural residues.